Mechanisms of drug-induced anaphylaxis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely distributed and frequently prescribed as mild analgesics and antipyretics for various types of pain. Systemic hypersensitivity reactions to NSAIDs represent one type of possible adverse drug reactions, but may have potentially life-threatening consequences. Notably, the mechanism of hypersensitivity reactions often remains unclear due to the lack of appropriate diagnostic means, and a differentiation between allergic and pseudoallergic adverse reaction can not be made unequivocally. We will investigate the mechanism of systemic hypersensitivity to the NSAID diclofenac. We will investigate the immune interactions of diclofenac by histamine release and human serology. Metabolites will be tested in addition to diclofenac and alternative means of conjugating diclofenac to human serum albumin will be investigated. We aim to develop an in vitro diagnostic test system and assess its clinical applicability in collaboration with two major allergy centers in Austria. As mouse models have repeatedly proven to be versatile instruments in allergy research, we will use immunization protocols capable of inducing an immune response resembling the in vivo situation in humans for the establishment of a mouse model for diclofenac allergy. We will furthermore apply proteomic methods to identify serum proteins being haptenized by diclofenac and study novel immune interactions.